Suppression of autoimmune neuritis in IFN-gamma receptor-deficient mice

Experimental autoimmune neuritis (EAN) is an animal model of the human dise ase Guillain-Barre syndrome, In this autoimmune inflammatory disease, CD4() T cells mediate demyelination in the peripheral nervous system (PNS), Inf iltrating macrophages and T cells as well as cytokines like interferon (IFN )-gamma are intimately involved in causing pathogenic effects, To investiga te the role of IFN-gamma in cell-mediated EAN, IFN-gamma receptor-deficient mutant (IFN-gammaR(-/-)) C57BL/6 mice and corresponding wild-type mice wer e immunized with PO peptide 180-199, a purified component of peripheral ner ve myelin, and Freund's complete adjuvant, IFN-gammaR(-/-) mice exhibited l ater onset of clinical disease. The disease was also less severe than in wi ld-type mice, Fewer IL-18-producing but more IL-4-producing cells were foun d in sciatic nerve sections from IFN-gammaR(-/-) mice than from wild-type m ice on day 24 postimmunization, i.e., at the peak of clinical EAN, At the s ame time, IFN-gammaR(-/-) mice had less infiltration of inflammatory cells, including macrophages, CD4(+) T cells, and monocytes, into sciatic nerve t issue and less demyelination, However, numbers of IFN-gamma -secreting cell s from the spleen were significantly augmented in the IFN-gammaR(-/-) mice, reflecting a failure of negative feedback circuits. The IFN-gammaR deficie ncy did not affect the production of anti-P0 peptide 180-199-specific antib odies, These results indicate that IFN-gamma contributes to a susceptibilit y for EAN in C57BL/6 mice by promoting a Th1 cell-mediated immune response and suppressing a Th2 response. (C) 2001 Academic Press.